Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy aftersurgery and as a chemopreventive agent in women of child-bearing age.However, TAM therapy has been shown to result in an increased incidence ofendometrial carcinoma in women. The present study was designed toinvestigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g.to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on theirfemale offspring. Progressive proliferative hyperplasia of the oviduct wasfrequently seen in TAM-exposed offspring, reaching 100% incidence by 52weeks in both treatment groups. These females also developed progressiveproliferative uterine lesions, including moderate/severe cystic endometrialhyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) whileleiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa celltumors (14%), were found between 72 and 78 weeks. Our findings thus suggesta strong association between transplacental TAM and reproductive tractabnormalities in female CD-1 mice.